Stroke is the third leading cause of death in the United States and otherwise a frequently disabling neurologic condition. The American Heart Association estimates an annual stroke incidence of 500,000 new patients and prevalence of 4 million stroke survivors. Many of these patients require chronic rehabilitation and specialized care, and frequently require long-term hospitalization.
Cerebral embolic stroke represents approximately 10-24% of all stroke types, the remainder of which are atherothrombotic or hemorrhagic in origin. Mechanisms responsible for particle embolization from cardiac structures to the cranial circulation include thrombosis from flow stagnation secondary to arrhythmias and post-myocardial infarction left ventricular dysfunction, intracardiac mechanical prosthesis-blood interface coagulation activation, infective or non-infective endocarditis, and instrument thrombosis related to left-sided endocardial ablations, valvuloplasties, and transcatheter valve replacements.
Current therapies targeting the pro-thrombotic state of atrial arrhythmias include chronic oral anticoagulation and more recently mechanical isolation of the thrombus-prone left atrial appendage for patients deemed to have elevated bleeding risk. Mainstay oral anticoagulation involves variable-dose daily medication with weekly to monthly serum level surveillance for therapeutic effect. Novel anticoagulation with set dosing and no blood level surveillance has recently entered clinical practice, although currently no reversal agents exist in the event of catastrophic bleeding complications. Left atrial appendage occlusion or isolation devices target the essential elimination of the structure most recognized as a culprit region with flow stagnation in atrial arrhythmias, ultimately leading to thrombus formation and potential dislodgment and embolization to the cranial circulation, i.e. stroke. These devices either fill the structural void of the appendage from an intracardiac plug approach, or ligate the segment from a combined epicardial approach such as that augmented with magnetic guidance.
Surgically implanted mechanical prosthetic intracardiac valves require lifelong oral anticoagulation to halt the coagulation cascade and resulting thrombosis activated at the device interface. Under certain clinical circumstances such as bleeding, when reversal of anticoagulation is required to prevent excessive blood loss, the mechanical device in contact with the patient's circulating blood becomes particularly susceptible to thrombosis, and again, embolization leading to potential stroke.
Transcatheter aortic valve replacement or implantation (TAVR/TAVI) is gaining popularity as a minimally invasive alternative method for treating severe aortic stenosis (AS) in patients deemed to have prohibitive surgical risk. TAVR is a procedure whereby a catheter-loaded bio-prosthetic aortic valve is delivered either percutaneously via peripheral arteries or surgically via a mini-thoracotomy with trans-apical or trans-aortic approach to the native aortic valve region, following balloon valvuloplasty. The most significant adverse outcome associated with this approach is stroke, both at the time of procedure and up to 2 years post-procedure, despite dual antiplatelet therapy.
The Placement of Aortic Trans-catheter Valves (PARTNER) trial, published in 2010 in The New England Journal of Medicine, found that in high-risk patients with symptomatic severe AS, including those deemed unsuitable candidates for surgery, TAVR, as compared to standard therapy (i.e. balloon valvuloplasty), significantly reduced cardiac symptoms, repeat hospitalization, and all-cause mortality. However, this trial revealed a higher incidence of major strokes and vascular events with TAVR, at both thirty days and one year post-implant. Follow-up data from this trial has demonstrated persisting stroke risk beyond 2 years. Both subclinical athero-embolization (detected by diffusion-weighted magnetic resonance imaging of the brain) and clinically evident stroke are potential complications of TAVR, and carry the greatest implications in patient outcome and peri-procedural cost from additional care and hospitalization. Proposed mechanisms for increased risk of embolic events during and after TAVR include the aortic luminal trauma during catheter and device transit, balloon valvuloplasty, deployment-related mechanical disruption of the aorta and native aortic valve causing fragmentation and embolization, potential valvular micro-thrombi, and atrial fibrillation (AF) following TAVR.
Additionally, left-sided or systemic circulation endocardial ablation procedures target elimination of electrophysiologic channels, pathways, and foci responsible for arrhythmias including atrial fibrillation, atypical left-sided flutter, atrial tachycardia, bypass tracts, and ventricular tachycardia. These procedures require either trans-septal or trans-aortic instrument transit to targeted ablation site, exposing instrument surfaces to blood, and yielding potential for thrombus formation and embolic events.